ArticleHuman molecular genetics2018
Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Article
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- Genetic Signatures of Competitive Performance in Burmese Gamecocks: A Transcriptomic Analysis.Biology · 2025Article
- Transcriptomic pathology of neocortical microcircuit cell types across psychiatric disorders.Molecular psychiatry · 2025Article
- The role of interleukin-37 and interleukin-38 in the development and remission of autism spectrum disorder: a comprehensive review of neuroinflammatory mechanisms and potential therapeutic implications.Frontiers in immunology · 2025Review
- Use of a predictor cue during a speech sound discrimination task in a Cntnap2 knockout rat model of autism.PloS one · 2025Article
- Initial regional cytoarchitectonic differences in dorsal and orbitobasal human developing frontal cortex revealed by spatial transcriptomics.Brain structure & function · 2024Article
- nlr-1/CNTNAP regulates dopamine circuit structure and foraging behaviors in C. elegans.Communications biology · 2024Article
- Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes.Signal transduction and targeted therapy · 2024Article
- Low Plasma Levels of Contactin-Associated Protein-Like 2 in Children with Autism Spectrum Disorder: Links to Neural Development.Neuropsychiatric disease and treatment · 2024Article
- Heterozygous deletion of the autism-associated gene CHD8 impairs synaptic function through widespread changes in gene expression and chromatin compaction.American journal of human genetics · 2023Article
- The NO Answer for Autism Spectrum Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Repurposing of Tibolone in Alzheimer's Disease.Biomolecules · 2023Review
- Genotype-phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder.Human genetics · 2023Review
- CNTNAP2 Protein Is Degraded by the Ubiquitin-Proteasome System and the Macroautophagy-Lysosome Pathway.Molecular neurobiology · 2023Article
- Maternal brain reactive antibodies profile in autism spectrum disorder: an update.Translational psychiatry · 2023Review
- Cntnap2-dependent molecular networks in autism spectrum disorder revealed through an integrative multi-omics analysis.Molecular psychiatry · 2023Article
- Non-coding RNAs associated with Prader-Willi syndrome regulate transcription of neurodevelopmental genes in human induced pluripotent stem cells.Human molecular genetics · 2023Article
- Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation.Frontiers in molecular neuroscience · 2023Article
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10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro. Loss of one Cntnap2 allele is sufficient to elicit axonal growth alteration, revealing a situation that may be relevant for CNTNAP2 heterozygosity in ASD patients. Then, we show that the two ASD variants I869T and G731S, which present impaired binding to Contactin2/TAG-1, do not rescue axonal growth deficits. We find that the variant R1119H leading to protein trafficking defects and retention in the endoplasmic reticulum has a dominant-negative effect on heterozygous Cntnap2 cortical neuron axon growth, through oligomerization with wild-type Caspr2. Finally, we identify an additional variant (N407S) with a dominant-negative effect on axon growth although it is well-localized at the membrane and properly binds to Contactin2. Thus, our data identify a new neurodevelopmental function for Caspr2, the dysregulation of which may contribute to clinical manifestations of ASD, and provide evidence that CNTNAP2 heterozygous missense variants may contribute to pathogenicity in ASD, through selective mechanisms.
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